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PMID:11487638

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Citation

Menet, V, Giménez y Ribotta, M, Chauvet, N, Drian, MJ, Lannoy, J, Colucci-Guyon, E and Privat, A (2001) Inactivation of the glial fibrillary acidic protein gene, but not that of vimentin, improves neuronal survival and neurite growth by modifying adhesion molecule expression. J. Neurosci. 21:6147-58

Abstract

Intermediate filaments (IFs) are a major component of the cytoskeleton in astrocytes. Their role is far from being completely understood. Immature astrocytes play a major role in neuronal migration and neuritogenesis, and their IFs are mainly composed of vimentin. In mature differentiated astrocytes, vimentin is replaced by the IF protein glial fibrillary acidic protein (GFAP). In response to injury of the CNS in the adult, astrocytes become reactive, upregulate the expression of GFAP, and reexpress vimentin. These modifications contribute to the formation of a glial scar that is obstructive to axonal regeneration. Nevertheless, astrocytes in vitro are considered to be the ideal substratum for the growth of embryonic CNS axons. In the present study, we have examined the potential role of these two major IF proteins in both neuronal survival and neurite growth. For this purpose, we cocultured wild-type neurons on astrocytes from three types of knock-out (KO) mice for GFAP or/and vimentin in a neuron-astrocyte coculture model. We show that the double KO astrocytes present many features of immaturity and greatly improve survival and neurite growth of cocultured neurons by increasing cell-cell contact and secreting diffusible factors. Moreover, our data suggest that the absence of vimentin is not a key element in the permissivity of the mutant astrocytes. Finally, we show that only the absence of GFAP is associated with an increased expression of some extracellular matrix and adhesion molecules. To conclude, our results suggest that GFAP expression is able to modulate key biochemical properties of astrocytes that are implicated in their permissivity.

Links

PubMed

Keywords

Animals; Astrocytes/metabolism; Astrocytes/ultrastructure; Cadherins/metabolism; Cell Adhesion/physiology; Cell Count; Cell Survival/genetics; Cells, Cultured; Coculture Techniques; Extracellular Matrix/metabolism; Fibronectins/metabolism; Gene Targeting; Glial Fibrillary Acidic Protein/biosynthesis; Glial Fibrillary Acidic Protein/deficiency; Glial Fibrillary Acidic Protein/genetics; Intermediate Filament Proteins/biosynthesis; Intermediate Filaments/metabolism; Intermediate Filaments/ultrastructure; Mice; Mice, Inbred Strains; Mice, Knockout; Models, Biological; Nerve Tissue Proteins; Neural Cell Adhesion Molecules/biosynthesis; Neural Cell Adhesion Molecules/metabolism; Neurites/metabolism; Neurites/ultrastructure; Neurons/cytology; Neurons/metabolism; Vimentin/biosynthesis; Vimentin/deficiency; Vimentin/genetics

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

MOUSE:GFAP

acts_upstream_of_or_within

GO:0030198: extracellular matrix organization

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2183221

P

  • occurs_in:(EMAPA:17544)

Seeded From UniProt

complete

MOUSE:GFAP

acts_upstream_of_or_within

GO:0010977: negative regulation of neuron projection development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2183221

P

  • regulates_o_occurs_in:(CL:0000117)
  • regulates_o_occurs_in:(EMAPA:17544)

Seeded From UniProt

complete

MOUSE:GFAP

acts_upstream_of_or_within

GO:0010977: negative regulation of neuron projection development

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:98932

P

  • regulates_o_occurs_in:(CL:0000117)
  • regulates_o_occurs_in:(EMAPA:17544)

Seeded From UniProt

complete

MOUSE:GFAP

located_in

GO:0005882: intermediate filament

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(CL:0000127)
  • part_of:(EMAPA:17577)

Seeded From UniProt

complete

MOUSE:GFAP

acts_upstream_of_or_within

GO:0045109: intermediate filament organization

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:98932

P

  • occurs_in:(CL:0000127)
  • occurs_in:(EMAPA:17544)

Seeded From UniProt

complete

MOUSE:VIME

acts_upstream_of_or_within

GO:0010977: negative regulation of neuron projection development

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:95697

P

  • regulates_o_occurs_in:(CL:0000117)
  • regulates_o_occurs_in:(EMAPA:17544)

Seeded From UniProt

complete

MOUSE:VIME

located_in

GO:0005882: intermediate filament

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(CL:0000127)
  • part_of:(EMAPA:17577)

Seeded From UniProt

complete

MOUSE:VIME

acts_upstream_of_or_within

GO:0045109: intermediate filament organization

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:95697

P

  • occurs_in:(CL:0000127)
  • occurs_in:(EMAPA:17544)

Seeded From UniProt

complete

MOUSE:GFAP

acts_upstream_of_or_within

GO:0030198: extracellular matrix organization

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2183221

P

Seeded From UniProt

complete

MOUSE:GFAP

part_of

GO:0005882: intermediate filament

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(EMAPA:17577)
  • part_of:(CL:0000127)

Seeded From UniProt

complete

MOUSE:GFAP

acts_upstream_of_or_within

GO:0045109: intermediate filament organization

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:98932

P

  • occurs_in:(EMAPA:17544)
  • occurs_in:(CL:0000127)

Seeded From UniProt

complete

MOUSE:GFAP

acts_upstream_of_or_within

GO:0010977: negative regulation of neuron projection development

ECO:0000315: mutant phenotype evidence used in manual assertion

MGI:MGI:2183221

P

  • regulates_o_occurs_in:(EMAPA:17544)
  • regulates_o_occurs_in:(CL:0000117)

Seeded From UniProt

complete

MOUSE:GFAP

acts_upstream_of_or_within

GO:0010977: negative regulation of neuron projection development

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:98932

P

  • regulates_o_occurs_in:(EMAPA:17544)
  • regulates_o_occurs_in:(CL:0000117)

Seeded From UniProt

complete

MOUSE:GFAP

acts_upstream_of_or_within

GO:0014002: astrocyte development

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:98932

P

  • occurs_in:(EMAPA:17544)
  • results_in_development_of:(CL:0000127)

Seeded From UniProt

complete

MOUSE:VIME

acts_upstream_of_or_within

GO:0045109: intermediate filament organization

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:95697

P

  • occurs_in:(EMAPA:17544)
  • occurs_in:(CL:0000127)

Seeded From UniProt

complete

MOUSE:VIME

part_of

GO:0005882: intermediate filament

ECO:0000314: direct assay evidence used in manual assertion

C

  • part_of:(EMAPA:17577)
  • part_of:(CL:0000127)

Seeded From UniProt

complete

MOUSE:VIME

acts_upstream_of_or_within

GO:0010977: negative regulation of neuron projection development

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:95697

P

  • regulates_o_occurs_in:(EMAPA:17544)
  • regulates_o_occurs_in:(CL:0000117)

Seeded From UniProt

complete

MOUSE:VIME

acts_upstream_of_or_within

GO:0014002: astrocyte development

ECO:0000316: genetic interaction evidence used in manual assertion

MGI:MGI:95697

P

  • occurs_in:(EMAPA:17544)
  • results_in_development_of:(CL:0000127)

Seeded From UniProt

complete


See also

References

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